Different mechanisms of CD200-CD200R induce diverse outcomes in cancer treatment
Bibliographic record
Abstract
The CD200 is a cell membrane protein expressed by tumor cells, and its receptor CD200 receptor (CD200R) is expressed by immune cells including macrophages and dendritic cells. The formation of CD200-CD200R inhibits the cellular functions of the targeted immune cells, so CD200 is one type of the immune checkpoint and blockade CD200-CD200R formation is a potential cancer treatment. However, the CD200 blockade has opposite treatment outcomes in different types of cancers. For instance, the CD200R deficient mice have a higher tumor load than the wild type (WT) mice in melanoma suggesting that CD200-CD200R inhibits melanoma. On the other hand, the antibody anti-CD200 treatment in pancreatic ductal adenocarcinoma (PDAC) and head and neck squamous cell carcinoma (HNSCC) significantly reduces the tumor load indicating that CD200-CD200R promotes PDAC and HNSCC. In this work, we hypothesize that different mechanisms of CD200-CD200R in tumor microenvironment could be one of the reasons for the diverse treatment outcomes of CD200 blockade in different types of cancers. We create one Ordinary Differential Equations (ODEs) model for melanoma including the inhibition of CCL8 and regulatory T cells and the switching from M2 to M1 macrophages by CD200-CD200R to capture the tumor inhibition by CD200-CD200R. We also create another ODEs model for PDAC and HNSCC including the promotion of the polarization and suppressive activities of M2 macrophages by CD200-CD200R to generate the tumor promotion by CD200-CD200R. Furthermore, we use these two models to investigate the treatment efficacy of the combination treatment between the CD200-CD200R blockade and the other immune checkpoint inhibitor, anti-PD-1. Our result shows that different mechanisms of CD200-CD200R can induce different treatment outcomes in combination treatments, namely, only the CD200-CD200R blockade reduces tumor load in melanoma and only the anti-PD-1 and CD200 knockout decrease tumor load in PDAC and HNSCC. Moreover, in melanoma, the CD200-CD200R mainly utilizes the inhibitions on M1 macrophages and dendritic cells to inhibit tumor growth, instead of M2 macrophages.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".